Myotubuler myopathy (MTM) is a rare and severe X-linked muscle disorder that occurs with an estimated incidence of 1 male in every 50,000 births. Myotubular myopathy is a member of a category of diseases referred to as centronuclear myopathies. A cardinal feature of centronuclear myopathies is that the nucleus is positioned in the center of many of the affected individual's muscle cells, rather than in the normal location at the ends of these cells. Although centronuclear myopathies share this characteristic feature, the various diseases have different causes, afflict different patient populations, and have unique disease progression and prognosis.
Myotubular myopathy is caused by a deficiency of the myotubularin 1 (MTM1) protein, a phosphoinositide phosphatase (Bello A B et al., Human Molecular Genetics, 2008, Vol, 17, No. 14), At birth MTM patients present with severe hypotonia and respiratory distress and those that survive the neonatal period are often totally or partially dependent upon ventilator support (Taylor G S et al., Proc Natl Acad Sci USA. 2000 August 1; 97(16):8910-5; Bello A B et al., Proc Natl Acad Sci USA. 2002 November 12; 99(23):15060-5; Pierson C R et al., Neuromuscul Disord. 2007 July; 17(7): 562-568; Herman G E et al., THE JOURNAL OF PEDIATRICS VOLUME 134, NUMBER 2). Patients with MTM exhibit delayed motor milestones and are susceptible to complications such as scoliosis, malocclusion, pyloric stenosis, spherocytosis, and gall and kidney stones, yet linear growth and intelligence are normal and the disease follows a non-progressive course (Herman G E et al., THE JOURNAL OF PEDIATRICS VOLUME 134, NUMBER 2). The average hospital stay for neonatal MTM patients is ˜90 days. However, patients that survive will require long-term ventilatory assistance and in-home care. The cost of basic supportive care, as well as the costs associated with handling the medical complications that often arise in MTM patients, impose a substantial personal and economic burden on patients and families.